The overall objective of this research proposal is to investigate the interactions of corneal and conjunctival cellular populations and cytokines in both healthy and disease states. The experiments are designed to test the hypothesis that complex interactions at these sites are highly integrated and are just as important in maintaining a functionally and optically normal anterior segment as in dealing with perturbations including those eliciting immune responses. The research concentrates on dendritic Langerhans cells, corneal nerves and cytokines. Models of immune mediated responses, corneal wound healing, transplantation and denervation will be studied by immunological, immunohistochemical using cell surface marker and substance P-like immunoreactivity and physiological assays. The cytokines to be studied in most detail will be IL-l, IFN-delta nerve growth factor and tissue plasminogen activator. The studies will be conducted in inbred strains of mice and rats, and outbred rabbits. The Specific Aims of the proposal are (1) Examine the alteration of histocompatibility antigen expression on cell surfaces in perturbed cornea. (2) Examine the role(s) of corneal nerves and ocular surface Langerhans cells in immune and physiological responses. (3) Examine and define the maturational and functional status of cellular populations in the ocular surface, especially Langerhans cells. (4) Devise specific methods or therapies to favorably influence ocular surface phenomena (e.g., wound healing, avoidance of allograft rejection, downregulating immune responses). The results of this research will help define more specific methods for promoting wound healing, controlling immune responses and tissue degradation as well as avoiding allograft rejection.